Optical activity (OA) along the optic axis of crystalline benzil has been measured by many over the past 150 years. However, the OA anisotropy remains uncharacterized due to difficulties in sample preparation as well as competition with linear birefringence (LB). The challenges associated with measuring OA along low-symmetry directions in crystals have too often left scientists with only average values of nonresonant OA in solution, i.e., specific rotations, which continue to resist interpretation in terms of structure. Measuring OA anisotropy has been facilitated by recent advances in polarimetry and optical modeling and here we compare results from two distinct division-of-time polarimeters. The absolute structure of crystalline benzil was established for the first time. The optical rotation (OR) of (+)-crystalline benzil (space group P3(1)21) perpendicular to the optic axis at the sodium D-line is -24.6 +/- 1.1 degrees/mm. A spectroscopic optical model in the transparent region of the crystal is provided. Electronic structure calculations of OR inform the polarimetric measurements and point to the necessity of developing linear response theory with periodic boundary conditions in order to interpret the results of chiroptical measurements in crystals.

Sensing technology for biomolecules has played a key role for maintaining a high quality of life. Various kinds of sensing techniques have been developed for detecting biomolecules. Among the detection techniques which have been reported so far, non-enzymatic glucose detection, based on electrochemical mechanisms, has attracted great interest as a facile route for monitoring glucose levels in the blood. In this method, designing nanostructured electrodes is a promising strategy to improve detection performance. Owing to their fascinating physicochemical properties, including superior electrical and electrocatalytic properties, mesoporous metal films offer a wide range of useful applications which cannot be achieved by other mesoporous materials. In this work, mesoporous Au films (MpGFs) are synthesized by an effective and simple electrochemical process in the presence of a surfactant, where the mesoporous structure can be controlled by the size of the polymeric micelles. The micelles are removed using a tetrahydrofuran-based solvent-extraction method. The activity of MpGFs towards glucose oxidation is evaluated under a fixed potential in alkaline solution. Under optimal potentials, the current response for other interfering molecules is minimal, while the current response for glucose is maximal. A linear relationship between the current response and the glucose content is observed over a wide range of concentrations. Thus, our MpGF shows an excellent performance for electrochemical glucose sensing applications.

We previously succeeded to prepare stable mesoporous Cu films on Au-coated conductive working electrodes by using polystyrene-b-poly(oxyethylene) (PS63000-b-PEO26000) micelles as template and sulfuric acid to increase ionic conductivity. In the present study, we report the preparation of mesoporous Cu films on Cu foil. By changing the Cu salts and electrodeposition potentials, we discuss how these parameters influence the final product. Without having to filtrate interefering species, such as uric acid, ascorbic acid and glucose, the dopamine concentration can be precisely determined by applying a suitable potential. Therefore, non-invasive electrochemical sensing based on mesoporous films will be useful for daily diagnosis of mental disorder.

Mesoporous metals that combine catalytic activity and high surface area can provide more opportunities for electrochemical applications. Various synthetic methods, including hard and soft templating, have been developed to prepare mesoporous/nanoporous metals. Micelle assembly, typically involved in soft-templates, is flexible and convenient for such purposes. It is, however, difficult to control, and the ordering is significantly destroyed during the metal deposition process, which is detrimental when it comes to designing precisely mesostructured materials. In the present work, mesoporous Pd films were uniformly electrodeposited using a nonionic surfactant, triblock copolymer poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), as a pore-directing agent. The interaction between micelles and metal precursors greatly influences the metal growth and determines the final structure. The water-coordinated species interact with the ethylene oxide moiety of the micelles to effectively drive the Pd(II) species toward the working electrode surface. From small-angle neutron scattering data, it is found that spherical P123 micelles, with an average diameter of similar to 14 nm, are formed in the electrolyte, and the addition of Pd ions does not significantly modify their structure, which is the essence of the micelle assembly approach. The uniformly sized mesopores are formed over the entire mesoporous Pd film and have an average pore diameter of 10.9 nm. Cross-sectional observation of the film also shows mesopores spanning continuously from the bottom to the top of the film. The crystallinity, crystal phase, and electronic coordination state of the Pd film are also confirmed. Through this study, it is found that the optimized surfactant concentration and applied deposition potential are the key factors to govern the formation of homogeneous and well-distributed pores over the entire film. Interestingly, the as-prepared mesoporous Pd films exhibit superior electrocatalytic activity toward the ethanol oxidation reaction by fully utilising the accessible active surface area. Our approach combines electrochemistry with colloidal and coordination chemistry and is widely applicable to other promising metals and alloy electrocatalysts.

Mesoporous Pd@Pt nanoparticles possess high surface areas while still maintaining electroconductivity and low potential for agglomeration. By introducing L-or D-DOPA (3,4-dihydroxyphe-nylalanine) enantiomers during the synthesis of the mesoporous Pd@Pt nanoparticles, we can create a Pt shell that is sensitive to the chirality of the DOPA molecule. We demonstrate sensitive electrochemical detection of DOPA enantiomers.

© 2017 Wiley Periodicals, Inc. Enantiomeric thalidomide undergoes various kinds of biotransformations including chiral inversion, hydrolysis, and enzymatic oxidation, which results in several metabolites, thereby adding to the complexity in the understanding of the nature of thalidomide. To decipher this complexity, we analyzed the multidimensional metabolic reaction networks of thalidomide and related molecules in vitro. Characteristic patterns in the amount of various metabolites of thalidomide and related molecules generated during a combination of chiral inversion, hydrolysis, and hydroxylation were observed using liquid chromatography–tandem mass spectrometry and chiroptical spectroscopy. We found that monosubstituted thalidomide derivatives exhibited different time-dependent metabolic patterns compared with thalidomide. We also revealed that monohydrolyzed and monohydroxylated metabolites of thalidomide were likely to generate mainly by a C-5 oxidation of thalidomide and subsequent ring opening of the hydroxylated metabolite. Since chirality was conserved in most of these metabolites during metabolism, they had the same chirality as that of nonmetabolized thalidomide. Our findings will contribute toward understanding the significant pharmacological effects of the multiple metabolites of thalidomide and its derivatives.

Wavelength dependence measurements of the chiroptical properties in alanine crystals have so far been unsuccessful using conventional spectroscopic techniques. We describe our attempts to measure the wavelength dependence of the optical activity in L- and D-alanine crystals along each crystallographic axis, and to determine the absolute chirality of alanine crystals by correlating the absolute structure to the optical activity using an x-ray diffractometer and a generalized high accuracy universal polarimeter. We have succeeded in accurately measuring the optical rotatory dispersion in the < 010 > direction, which shows that the optical rotation of the n-alanine crystal is dextrorotatory and that of the L-alanine crystal is laevorotatory, thereby determining the absolute chirality. Furthermore, comparison with the optical activity in solution shows that the optical activity in alanine crystals is different not only in value, but also in the sign. These results have led us to conclude that the optical rotatory power in the crystalline state should not be simply the summation of molecular optical rotatory power values. We propose the necessity of a theory, which contains the contribution of molecular interactions within the crystal, in order to calculate the optical rotatory power of the crystalline state.

A fast, high-accuracy universal polarimeter was developed using a charge-coupled device (CCD) spectrometer (CCD-HAUP), to carry out simultaneous optical anisotropic (linear birefringence, LB; linear dichroism, LD) and chiroptical (circular birefringence, CB; circular dichroism, CD) measurements on single crystals without any pretreatment, in the visible region between 400-680 nm. The principle of the HAUP method is to measure the intensities of emergent light passing through a polarizer, a crystal sample, and then an analyzer, as the azimuth angles of the polarizer and analyzer are independently altered. The CCD-HAUP has the unique feature that white transmitted light intensity can be measured using a CCD spectrometer, compared with the generalized HAUP (G-HAUP) system in which monochromatic transmitted light is measured using a photomultiplier. The CCD-HAUP measurements across the entire wavelength region are completed within the G-HAUP measurement time for a single wavelength. The CCD-HAUP drastically reduces the measurement time for a dataset to only 1.5 h, from the 24 h required for the G-HAUP system. LB, LD, CB, and CD measurements of single crystals of alpha-quartz and enantiomeric photomechanical sali-cylidenephenylethylamines before, during, and after ultraviolet light irradiation show results comparable to those obtained using the G-HAUP system. The newly developed system is very effective for samples susceptible to degradation induced by external stimuli, such as light and heat. (C) 2017 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

The chiral crystal of enantiomeric (S)-N-3,5-di-tert-butylsalicylidene-1-phenylethylamine in the enol form [enol-(S)-1] undergoes a reversible single-crystal-to-single-crystal (SCSC) phase transition at T-c approximate to 3 degrees C from the room temperature beta-form in orthorhombic space group P2(1)2(1)2(1) (Z' = 1) to the low temperature -form in the monoclinic space group P2(1) (Z' = 2) with a thermal hysteresis of approximately 1.7 degrees C. A detailed comparison of the crystal structures of the alpha- and beta-forms revealed that the 5-tert-butyl group of one molecule in the asymmetric unit of the beta-form rotated by ca. 60 degrees, and the dihedral angle between the phenyl and salicyl planes increased slightly in the beta-form crystal. However, the changes in the molecular conformation and packing arrangement are small, which leads to the reversible SCSC phase transition with no destruction of the crystal lattice. The dielectric constant along the b-axis was small, probably due to the weak intermolecular interactions in the crystals.

Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that is highly conserved in animals and plants. CRBN proteins have been implicated in various biological processes such as development, metabolism, learning, and memory formation, and their impairment has been linked to autosomal recessive non-syndromic intellectual disability and cancer. Furthermore, human CRBN was identified as the primary target of thalidomide teratogenicity. Data on functional analysis of CRBN family members in vivo, however, are still scarce. Here we identify Ohgata (OHGT), the Drosophila ortholog of CRBN, as a regulator of insulin signaling-mediated growth. Using ohgt mutants that we generated by targeted mutagenesis, we show that its loss results in increased body weight and organ size without changes of the body proportions. We demonstrate that ohgt knockdown in the fat body, an organ analogous to mammalian liver and adipose tissue, phenocopies the growth phenotypes. We further show that overgrowth is due to an elevation of insulin signaling in ohgt mutants and to the down-regulation of inhibitory cofactors of circulating Drosophila insulin-like peptides (DILPs), named acid-labile subunit and imaginal morphogenesis protein-late 2. The two inhibitory proteins were previously shown to be components of a heterotrimeric complex with growth-promoting DILP2 and DILP5. Our study reveals OHGT as a novel regulator of insulin-dependent organismic growth in Drosophila.

Introducing chirality into photomechanical crystals is beneficial for the diversification of mechanical motion. Measurement of the chiroptical and optical anisotropic properties of chiral crystals is indispensable for evaluating photomechanical crystals. The platelike crystals of S- and R-enantiomers of photochromic N-3,5-di-tert-butylsalicylidene-1-phenylethylamine in enol form (enol-(S)-1 and enol-(R)-1) caused bending motion with twisting upon ultraviolet (UV) light irradiation, due to shrinkage along the length and width directions of the irradiated surface, based on the optimized crystal structure of the photoisomerized trans-keto-(S)-1. By employing the generalized high-accuracy universal polarimeter (G-HAUP), optical anisotropic (linear birefringence, LB; linear dichroism, LD) as well as chiroptical (circular birefringence, CB; circular dichroism, CD) spectra of both the enantiomeric crystals on the (001) face were simultaneously measured before and under continuous UV irradiation. The LD peak was observed at 330 nm in the negative sign, derived from the pi-pi* transition of the intramolecularly hydrogen-bonded salicylidenimino moiety. The CD spectra of the S and R crystals revealed the negative and positive Cotton effect at 330 nm, respectively, and new peaks appeared at 460 rim under UV light irradiation due to photoisomerization to the S and R trans-keto isomers at around 10% conversion. The CB and CD spectra evaluated by the HAUP measurement were opposite to those measured in the hexane solution, as well as those simulated by quantum chemical calculation. The dissymmetry parameter, g, of the enol-(S)-1 crystal along the c axis (0.013) was approximately 10 times larger than the g values in the solution (0.0010) and by calculation (0.0016).

Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that is highly conserved in animals and plants. CRBN proteins have been implicated in various biological processes such as development, metabolism, learning, and memory formation, and their impairment has been linked to autosomal recessive non-syndromic intellectual disability and cancer. Furthermore, human CRBN was identified as the primary target of thalidomide teratogenicity. Data on functional analysis of CRBN family members in vivo, however, are still scarce. Here we identify Ohgata (OHGT), the Drosophila ortholog of CRBN, as a regulator of insulin signaling-mediated growth. Using ohgt mutants that we generated by targeted mutagenesis, we show that its loss results in increased body weight and organ size without changes of the body proportions. We demonstrate that ohgt knockdown in the fat body, an organ analogous to mammalian liver and adipose tissue, phenocopies the growth phenotypes. We further show that overgrowth is due to an elevation of insulin signaling in ohgt mutants and to the down-regulation of inhibitory cofactors of circulating Drosophila insulin-like peptides (DILPs), named acid-labile subunit and imaginal morphogenesis protein-late 2. The two inhibitory proteins were previously shown to be components of a heterotrimeric complex with growth-promoting DILP2 and DILP5. Our study reveals OHGT as a novel regulator of insulin-dependent organismic growth in Drosophila.

Introducing chirality into photomechanical crystals is beneficial for the diversification of mechanical motion. Measurement of the chiroptical and optical anisotropic properties of chiral crystals is indispensable for evaluating photomechanical crystals. The platelike crystals of S- and R-enantiomers of photochromic N-3,5-di-tert-butylsalicylidene-1-phenylethylamine in enol form (enol-(S)-1 and enol-(R)-1) caused bending motion with twisting upon ultraviolet (UV) light irradiation, due to shrinkage along the length and width directions of the irradiated surface, based on the optimized crystal structure of the photoisomerized trans-keto-(S)-1. By employing the generalized high-accuracy universal polarimeter (G-HAUP), optical anisotropic (linear birefringence, LB; linear dichroism, LD) as well as chiroptical (circular birefringence, CB; circular dichroism, CD) spectra of both the enantiomeric crystals on the (001) face were simultaneously measured before and under continuous UV irradiation. The LD peak was observed at 330 nm in the negative sign, derived from the pi-pi* transition of the intramolecularly hydrogen-bonded salicylidenimino moiety. The CD spectra of the S and R crystals revealed the negative and positive Cotton effect at 330 nm, respectively, and new peaks appeared at 460 rim under UV light irradiation due to photoisomerization to the S and R trans-keto isomers at around 10% conversion. The CB and CD spectra evaluated by the HAUP measurement were opposite to those measured in the hexane solution, as well as those simulated by quantum chemical calculation. The dissymmetry parameter, g, of the enol-(S)-1 crystal along the c axis (0.013) was approximately 10 times larger than the g values in the solution (0.0010) and by calculation (0.0016).

Solid-state photochemical reactions in crystals, known as topochemical reactions, are solvent-free green chemical reactions that produce stereospecific molecules. The photoreaction of thymine is interesting because the dimeric photoproduct can form four types of stereoisomers and when the dimer is formed in DNA helices it can cause skin cancers. We investigated the photoreaction of five multisubstituted thymine derivatives in the solid-state, which were designed with crystal engineering concepts to promote pi-pi stacking of benzene rings in the crystal. Powder X-ray diffraction analysis revealed that a para-substituted bis-thymine derivative was aligned along the c axis in the crystal and was susceptible to topochemical reaction to form a polymer, as previously reported. Ortho- and meta-substituted bis-thymine derivatives and a tetrakis-substituted derivative were found to be topochemically unreactive using both gel permeation chromatography (GPC) and X-ray crystal structural analysis. The tris-substituted thymine derivative was found to be topochemically reactive due to favorable crystal packing, which included ethanol molecules to form hydrogen bonding with one of the thymine moieties and stabilize the crystal packing. GPC and crystal structural analysis revealed that it could form tetramer at most via topochemical [2+2]-cycloaddition upon UV irradiation. Based on the crystal structure of the tris-substituted thymine derivative, the structure of the tetrameric photoproduct is expected to link via cis-syn, trans-anti and cis-syn cyclobutane isomers.

The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as a thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. (C) 2016 Elsevier Inc. All rights reserved.

Lon protease plays a major role in the protein quality control system in mammalian cell mitochondria. It is present in the mitochondrial matrix, and degrades oxidized and misfolded proteins, thereby protecting the cell from various extracellular stresses, including oxidative stress. The intellectual disability-associated and thalidomide-binding protein cereblon (CRBN) contains a large, highly conserved Lon domain. However, whether CRBN has Lon protease-like function remains unknown. Here, we determined if CRBN has a protective function against oxidative stress, similar to Lon protease. We report that CRBN partially distributes in mitochondria, suggesting it has a mitochondrial function. To specify the mitochondrial role of CRBN, we mitochondrially expressed CRBN in human neuroblastoma SH-SY5Y cells. The resulting stable SH-SY5Y cell line showed no apparent effect on the mitochondrial functions of fusion, fission, and membrane potential. However, mitochondrially expressed CRBN exhibited protease activity, and was induced by oxidative stress. In addition, stably expressed cells exhibited suppressed neuronal cell death induced by hydrogen peroxide. These results suggest that CRBN functions specifically as a Lon-type protease in mitochondria.

The photomechanical motion of chiral crystals of trans-azobenzene derivatives with an (S)- and (R)-phenylethylamide group was investigated and compared with a racemic crystal. Changes in the UV/Vis absorption spectra of the powdered crystals before and after UV irradiation were measured by using an optical waveguide spectrometer, showing that the lifetime of the cis-to-trans thermal backisomerization of the chiral crystals was faster than that of the racemic crystals. Upon UV irradiation, a long plate-like chiral microcrystal bent away from the light source with a twisting motion. A square-like chiral microcrystal curled toward the light with some twisting. Reversible bending of a rod-like chiral microcrystal was repeatable over twenty-five cycles. In contrast, bending of a plate-like racemic microcrystal was small. A possible mechanism for the bending and twisting motion was discussed based on the optimized cis conformer determined by using calculations, showing that the bending motion with twisting is caused by elongation along the b axis and shrinkage along the a axis.

Upon microwave irradiation, esterification of octanoic acid with 1-octanol in the presence of hydrochloric acid as an acid catalyst proceeded more efficiently in glass vessels than in silicon carbide (SiC) vessels, affording 1-octyl octanoate in higher yields and revealing microwave effects during esterification.

Achiral benzophenone is one of the simplest organic aromatic ketones that crystallize in the chiral form. The absolute structure of chiral crystals consisting of achiral benzophenone was firstly determined with single-crystal X-ray diffraction analysis and the absolute structure was successfully correlated with the solid-state circular dichroism spectra.

Achiral benzophenone is one of the simplest organic aromatic ketones that crystallize in the chiral form. The absolute structure of chiral crystals consisting of achiral benzophenone was firstly determined with single-crystal X-ray diffraction analysis and the absolute structure was successfully correlated with the solid-state circular dichroism spectra.

Polymer crystallization affects structural and mechanical properties of polymer thin films. In this study, we focused on the thermal annealing-induced crystallization in semi-crystalline poly(l-lactic acid) (PLLA) ultrathin films (referred as nanosheets) was investigated in terms of interfacial interaction of PLLA with air and substrate. The surface structure of the PLLA nanosheets observed by atomic force microscopy showed that roughness of the air-side surface increased due to crystallization of PLLA under thermal annealing, whereas that of the substrate-side surface changed little. The elastic moduli and the physical adhesiveness of the nanosheets also changed only on the surface of the air side from crystallization, in contrast to the substrate side. The X-ray diffraction studies of the PLLA nanosheets with different thickness showed that the crystalline contents steeply increased below ca. 200 nm. These results indicated that the crystallization was enhanced near the surface of the air side and restricted near that of the substrate side due to the different interfacial association of the polymer chains in the nanosheet.

Upon microwave irradiation, esterification of octanoic acid with 1-octanol in the presence of hydrochloric acid as an acid catalyst proceeded more efficiently in glass vessels than in silicon carbide (SiC) vessels, affording 1-octyl octanoate at higher yields and revealing microwave effects during esterification.

The photomechanical bending of crystals of a stilbene-type compound substituted with anthracene and indanone groups, (E)-2-(9-anthrylmethylene)-1-indanone (trans-1), was investigated. When a narrow plate-like microcrystal was irradiated with ultraviolet (UV) light at 365 nm, the crystal gradually bent away from the light source and finally reached a semicircular shape after more than 10 min. A larger rod-like crystal, approximately 10 mm in length, also exhibited a slight bending motion. The cessation of UV irradiation caused the bent crystals to return very slowly to their straight form. In the crystals, the anthracene planes of two neighbouring trans-1 molecules are arranged in a head-to-tail parallel manner, with a short plane-to-plane distance of only 3.72 angstrom. The H-1 nuclear magnetic resonance spectra of trans-1 crystals before and after UV irradiation revealed the intermolecular [4 + 4] photodimerisation of the two anthracene planes, while the trans-to-cis photoisomerisation was not significant. The UV-vis absorption spectra of the trans-1 powder crystals, obtained using a diffuse reflectance spectrophotometer, showed a gradual increase in absorbance between 200 and 500 nm with increasing UV irradiation time, reaching a maximum after 1 h. Thermal back-monomerisation was very slow in the dark, not recovering the initial spectrum even after 25 days. The fluorescence spectra at 570 nm, derived from the anthracene excimer, decreased in intensity with increasing UV irradiation time due to a decrease in the amount of anthracene chromophore via photodimerisation. In situ X-ray measurements revealed that the bending of the crystals was caused by slight elongation of the b axis of the unit cell, corresponding to the long axis of the rod-like crystals. Calculations revealed that the observed crystal elongation could be explained by an optimised head-to-tail [4 + 4] orientation of the anthracene dimer.

Cereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. In the presence of a proteasome inhibitor, exogenous CRBN formed perinuclear inclusions and co-localized with aggresome markers. Endogenous CRBN also formed perinuclear inclusions under the same condition. Treatment with a microtubule destabilizer or an inhibitor of the E3 ubiquitin ligase activity of CRBN blocked formation of CRBN inclusions. Biochemical analysis showed CRBN containing inclusions were high-molecular weight, ubiquitin-positive. CRBN overexpression in cultured cells suppressed cell death induced by proteasome inhibitor. Furthermore, knockdown of endogenous CRBN in cultured cells increased cell death induced by proteasome inhibitor, compared with control cells. Our results show CRBN is recruited to aggresome and has functional roles in cytoprotection against ubiquitin-proteasome system impaired condition.

Cereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. In the presence of a proteasome inhibitor, exogenous CRBN formed perinuclear inclusions and co-localized with aggresome markers. Endogenous CRBN also formed perinuclear inclusions under the same condition. Treatment with a microtubule destabilizer or an inhibitor of the E3 ubiquitin ligase activity of CRBN blocked formation of CRBN inclusions. Biochemical analysis showed CRBN containing inclusions were high-molecular weight, ubiquitin-positive. CRBN overexpression in cultured cells suppressed cell death induced by proteasome inhibitor. Furthermore, knockdown of endogenous CRBN in cultured cells increased cell death induced by proteasome inhibitor, compared with control cells. Our results show CRBN is recruited to aggresome and has functional roles in cytoprotection against ubiquitin-proteasome system impaired condition. (C) 2015 Elsevier Inc. All rights reserved.

Cereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. In the presence of a proteasome inhibitor, exogenous CRBN formed perinuclear inclusions and co-localized with aggresome markers. Endogenous CRBN also formed perinuclear inclusions under the same condition. Treatment with a microtubule destabilizer or an inhibitor of the E3 ubiquitin ligase activity of CRBN blocked formation of CRBN inclusions. Biochemical analysis showed CRBN containing inclusions were high-molecular weight, ubiquitin-positive. CRBN overexpression in cultured cells suppressed cell death induced by proteasome inhibitor. Furthermore, knockdown of endogenous CRBN in cultured cells increased cell death induced by proteasome inhibitor, compared with control cells. Our results show CRBN is recruited to aggresome and has functional roles in cytoprotection against ubiquitin-proteasome system impaired condition. (C) 2015 Elsevier Inc. All rights reserved.

In this study, systems of complicated pathways involved in chiral drug metabolism were investigated. The development of chiral drugs resulted in significant improvement in the remedies available for the treatment of various severe sicknesses. Enantiopure drugs undergo various biological transformations that involve chiral inversion and thus result in the generation of multiple enantiomeric metabolites. Identification of the specific active substances determining a given drug's efficacy among such a mixture of different metabolites remains a challenge. To comprehend this complexity, we constructed a mathematical model representing the complicated metabolic pathways simultaneously involving chiral inversion. Moreover, this model is applied to the metabolism of thalidomide, which has recently been revived as a potentially effective prescription drug for a number of intractable diseases. The numerical simulation results indicate that retained chirality in the metabolites reflects the original chirality of the unmetabolized drug, and a higher level of enantiomeric purity is preserved during spontaneous degradation. In addition, chirality remaining after equilibration is directly related to the rate constant not only for chiral inversion but also for generation and degradation. Furthermore, the retention of chirality is quantitatively predictable using this combination of kinetic parameters. Our simulation results well explain the behavior of thalidomide in the practical biological experimental data. Therefore, this model promises a comprehensive understanding of dynamic metabolic systems involving chiral drugs that express multiple enantiospecific drug efficacies. (C) 2015 Elsevier Ltd. All rights reserved.

In this study, systems of complicated pathways involved in chiral drug metabolism were investigated. The development of chiral drugs resulted in significant improvement in the remedies available for the treatment of various severe sicknesses. Enantiopure drugs undergo various biological transformations that involve chiral inversion and thus result in the generation of multiple enantiomeric metabolites. Identification of the specific active substances determining a given drug's efficacy among such a mixture of different metabolites remains a challenge. To comprehend this complexity, we constructed a mathematical model representing the complicated metabolic pathways simultaneously involving chiral inversion. Moreover, this model is applied to the metabolism of thalidomide, which has recently been revived as a potentially effective prescription drug for a number of intractable diseases. The numerical simulation results indicate that retained chirality in the metabolites reflects the original chirality of the unmetabolized drug, and a higher level of enantiomeric purity is preserved during spontaneous degradation. In addition, chirality remaining after equilibration is directly related to the rate constant not only for chiral inversion but also for generation and degradation. Furthermore, the retention of chirality is quantitatively predictable using this combination of kinetic parameters. Our simulation results well explain the behavior of thalidomide in the practical biological experimental data. Therefore, this model promises a comprehensive understanding of dynamic metabolic systems involving chiral drugs that express multiple enantiospecific drug efficacies. (C) 2015 Elsevier Ltd. All rights reserved.

:In this study, systems of complicated pathways involved in chiral drug metabolism were investigated. The development of chiral drugs resulted in significant improvement in the remedies available for the treatment of various severe sicknesses. Enantiopure drugs undergo various biological transformations that involve chiral inversion and thus result in the generation of multiple enantiomeric metabolites. Identification of the specific active substances determining a given drug׳s efficacy among such a mixture of different metabolites remains a challenge. To comprehend this complexity, we constructed a mathematical model representing the complicated metabolic pathways simultaneously involving chiral inversion. Moreover, this model is applied to the metabolism of thalidomide, which has recently been revived as a potentially effective prescription drug for a number of intractable diseases. The numerical simulation results indicate that retained chirality in the metabolites reflects the original chirality of the unmetabolized drug, and a higher level of enantiomeric purity is preserved during spontaneous degradation. In addition, chirality remaining after equilibration is directly related to the rate constant not only for chiral inversion but also for generation and degradation. Furthermore, the retention of chirality is quantitatively predictable using this combination of kinetic parameters. Our simulation results well explain the behavior of thalidomide in the practical biological experimental data. Therefore, this model promises a comprehensive understanding of dynamic metabolic systems involving chiral drugs that express multiple enantiospecific drug efficacies.

In the title compound, C&lt
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H&lt
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12&lt
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N&lt
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O&lt
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, the phthalimide ring system is essentially planar, with a maximum deviation of 0.0479 (14) Å. In the crystal, each molecule is linked via six neighbouring molecules into a three-dimensional network through N - H⋯O and O - H⋯O hydrogen bonds, which form an R &lt
inf&gt
3&lt
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sup&gt
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(8) ring motif.

We report on the self-disproportionation of enantiomers (SDE) of non-racemic thalidomide (1) and 3'-fluorothalidomide (2) under the conditions of gravity-driven achiral silica-gel chromatography. The presence of a fluorine atom on the chiral center dramatically alters the structure and polarity of 1 and 2, resulting in the opposite SDE profile on silica-gel.

Amyloid protein (A beta) plays a central role in the pathogenesis of Alzheimer's disease (AD). Point mutations within the A sequence associated with familial AD (FAD) are clustered around the central hydrophobic core of A. Several types of mutations within the A sequence have been identified, and the Arctic' mutation (E22G) has a purely cognitive phenotype typical of AD. Previous studies have shown that the primary result of the Arctic' mutation is increased formation of A protofibrils. However, the molecular mechanism underlying this effect remains unknown. A42 binds to a neuronal nicotinic acetylcholine receptor subunit, neuronal acetylcholine receptor subunit alpha-7 (CHRNA7), with high affinity and, thus, may be involved in the pathogenesis of AD. Therefore, to clarify the molecular mechanism of Arctic mutation-mediated FAD, we focused on CHRNA7 as a target molecule of Arctic A. We performed an in vitro binding assay using purified CHRNA7 and synthetic Arctic A40, and demonstrated that Arctic A40 specifically bound to CHRNA7. The aggregation of Arctic A40 was enhanced with the addition of CHRNA7. Furthermore, the function of CHRNA7 was detected by measuring Ca2+ flux and phospho-p44/42 MAPK (ERK1/2) activation. Our results indicated that Arctic A40 aggregation was enhanced by the addition of CHRNA7, which destabilized the function of CHRNA7 via inhibition of Ca2+ responses and activation of ERK1/2. These findings indicate that Arctic A mutation may be involved in the mechanism underlying FAD. This mechanism may involve binding and aggregation, leading to the inhibition of CHRNA7 functions.

To improve our ability to identify single crystals causing arthritis, we have developed a practical measurement system of polarized light microscopy called advanced compensated polarized light microscopy (A-CPLM). The A-CPLM system is constructed by employing a conventional phase retardation plate, an optical fibre and a charge-coupled device spectrometer in a polarized light microscope. We applied the A-CPLM system to measure linear birefringence (LB) in the visible region, which is an optical anisotropic property, for tiny single crystals causing arthritis, i.e. monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD). The A-CPLM system performance was evaluated by comparing the obtained experimental data using the A-CPLM system with (i) literature data for a standard sample, MgF2, and (ii) experimental data obtained using an established optical method, high-accuracy universal polarimeter, for the MSUM. The A-CPLM system was found to be applicable for measuring the LB spectra of the single crystals of MSUM and CPPD, which cause arthritis, in the visible regions. We quantitatively reveal the large difference in LB between MSUM and CPPD crystals. These results demonstrate the usefulness of the A-CPLM system for distinguishing the crystals causing arthritis.

:We propose, as an alternative to conventional spectroscopic assays, a simple method for discriminating fibrous amyloid proteins by using a label-free semiconductor-based biosensor. The highly sensitive assay is expected to be useful for accelerating amyloid related research.

A novel method for fabricating anisotropic collagen membranes, which regulate the preferred orientation, is developed. The high-accuracy universal polarimeter (HAUP) method is used for simultaneous and quantitative evaluations of the optical anisotropy and optical activity. The evaluation of these optical quantities, enabled by the HAUP method, is beneficial to the field of tissue engineering.

:A novel method for fabricating anisotropic collagen membranes, which regulate the preferred orientation, is developed. The high-accuracy universal polarimeter (HAUP) method is used for simultaneous and quantitative evaluations of the optical anisotropy and optical activity. The evaluation of these optical quantities, enabled by the HAUP method, is beneficial to the field of tissue engineering.

:Amyloid β protein (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). Point mutations within the Aβ sequence associated with familial AD (FAD) are clustered around the central hydrophobic core of Aβ. Several types of mutations within the Aβ sequence have been identified, and the 'Arctic' mutation (E22G) has a purely cognitive phenotype typical of AD. Previous studies have shown that the primary result of the 'Arctic' mutation is increased formation of Aβ protofibrils. However, the molecular mechanism underlying this effect remains unknown. Aβ42 binds to a neuronal nicotinic acetylcholine receptor subunit, neuronal acetylcholine receptor subunit alpha-7 (CHRNA7), with high affinity and, thus, may be involved in the pathogenesis of AD. Therefore, to clarify the molecular mechanism of Arctic mutation-mediated FAD, we focused on CHRNA7 as a target molecule of Arctic Aβ. We performed an in vitro binding assay using purified CHRNA7 and synthetic Arctic Aβ40, and demonstrated that Arctic Aβ40 specifically bound to CHRNA7. The aggregation of Arctic Aβ40 was enhanced with the addition of CHRNA7. Furthermore, the function of CHRNA7 was detected by measuring Ca(2+) flux and phospho-p44/42 MAPK (ERK1/2) activation. Our results indicated that Arctic Aβ40 aggregation was enhanced by the addition of CHRNA7, which destabilized the function of CHRNA7 via inhibition of Ca(2+) responses and activation of ERK1/2. These findings indicate that Arctic Aβ mutation may be involved in the mechanism underlying FAD. This mechanism may involve binding and aggregation, leading to the inhibition of CHRNA7 functions.

We propose, as an alternative to conventional spectroscopic assays, a simple method for discriminating fibrous amyloid proteins by using a label-free semiconductor-based biosensor. The highly sensitive assay is expected to be useful for accelerating amyloid related research.

A novel method for fabricating anisotropic collagen membranes, which regulate the preferred orientation, is developed. The high-accuracy universal polarimeter (HAUP) method is used for simultaneous and quantitative evaluations of the optical anisotropy and optical activity. The evaluation of these optical quantities, enabled by the HAUP method, is beneficial to the field of tissue engineering.

A metastable liquid crystal (LC) was found to serve as a time responsive reaction medium, in which the enantioselectivity of a photoreaction was perfectly switched through isothermal annealing of the reaction system. When the LC salt of an enantiopure amine with a photoreactive acid was irradiated with UV/vis light, in situ, photodimerization of the acid moiety proceeded smoothly to afford the (+)-isomer of the photodimer with high enantioselectivity (+86% ee). In contrast, photoirradiation of an aged sample, isothermally annealed for 20 h, gave predominantly the (-)-isomer (-94% ee). Systematic studies revealed that the reversal in selectivity originated from metastability. of the LC system, which gradually transformed into a crystalline phase during annealing. This finding demonstrates the potential use of metastable aggregates as dynamic time-responsive media, reminiscent of biological systems.

A metastable liquid crystal (LC) was found to serve as a time responsive reaction medium, in which the enantioselectivity of a photoreaction was perfectly switched through isothermal annealing of the reaction system. When the LC salt of an enantiopure amine with a photoreactive acid was irradiated with UV/vis light, in situ, photodimerization of the acid moiety proceeded smoothly to afford the (+)-isomer of the photodimer with high enantioselectivity (+86% ee). In contrast, photoirradiation of an aged sample, isothermally annealed for 20 h, gave predominantly the (-)-isomer (-94% ee). Systematic studies revealed that the reversal in selectivity originated from metastability. of the LC system, which gradually transformed into a crystalline phase during annealing. This finding demonstrates the potential use of metastable aggregates as dynamic time-responsive media, reminiscent of biological systems.

The proton motive force (PMF) is bio-energetically important for various cellular reactions to occur. We developed PMF-photogenerating mitochondria in cultured mammalian cells. An archaebacterial rhodopsin, delta-rhodopsin, which is a light-driven proton pump derived from Haloterrigena turkmenica, was expressed in the mitochondria of CHO-K1 cells. The constructed stable CHO-K1 cell lines showed suppression of cell death induced by rotenone, a pesticide that inhibits mitochondrial complex I activity involved in PMF generation through the electron transport chain. Delta-rhodopsin was also introduced into the mitochondria of human neuroblastoma SH-SY5Y cells. The constructed stable SH-SY5Y cell lines showed suppression of dopaminergic neuronal cell death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an inducer of Parkinson's disease models, which acts through inhibition of complex I activity. These results suggest that the light-activated proton pump functioned as a PMF generator in the mitochondria of mammalian cells, and suppressed cell death induced by inhibition of respiratory PMF generation.

Most polymers solidify below a glass transition temperature (;), which is important for the fabrication of polymeric materials. The glass transition dynamics (GTD) of polymers alters their physical properties and therefore the range of applications suitable for the particular materials. In this regard, most GTD studies were oriented to the thermodynamics of amorphous polymer systems, while little studies were known for semicrystalline polymers. Here, we focus on the glassy and crystalline properties of semicrystalline polymers such as poly(L-lactic acid) (PLLA) and envisage to control the nanostructure of free-standing PLLA ultrathin films (referred as "PLLA nanosheets"), via thermodynamic rearrangement of polymer chains entangled in a quasi-two-dimensional interface during the GTD process. The annealing process on the PLLA nanosheets (<100 nm thick) resulted in the formation of semicrystalline domains and microscopic apertures with polymer chains (similar to 100 nm in size). Such nanostructure surprisingly induced selective molecular permeability, which was controlled as a function of film thickness and inherent crystallinity. The present methodology demonstrates the direct conversion of thermodynamic properties of semicrystalline polymers into the functional nanostructured polymeric materials.

Most polymers solidify below a glass transition temperature (;), which is important for the fabrication of polymeric materials. The glass transition dynamics (GTD) of polymers alters their physical properties and therefore the range of applications suitable for the particular materials. In this regard, most GTD studies were oriented to the thermodynamics of amorphous polymer systems, while little studies were known for semicrystalline polymers. Here, we focus on the glassy and crystalline properties of semicrystalline polymers such as poly(L-lactic acid) (PLLA) and envisage to control the nanostructure of free-standing PLLA ultrathin films (referred as "PLLA nanosheets"), via thermodynamic rearrangement of polymer chains entangled in a quasi-two-dimensional interface during the GTD process. The annealing process on the PLLA nanosheets (<100 nm thick) resulted in the formation of semicrystalline domains and microscopic apertures with polymer chains (similar to 100 nm in size). Such nanostructure surprisingly induced selective molecular permeability, which was controlled as a function of film thickness and inherent crystallinity. The present methodology demonstrates the direct conversion of thermodynamic properties of semicrystalline polymers into the functional nanostructured polymeric materials.

The advanced high-accuracy universal polarimeter (HAUP) method was applied to observe anisotropic and chiroptical properties of an intercalated azobenzene derivative compound into K4Nb6O17 crystals. Prior to the HAUP measurement of the intercalated compound, we extended the HAUP method employing a conventional light source system composed of Xe or D-2 lamps and a monochromator instead of a laser system. The performance of the advanced HAUP system was evaluated and we determined the parasitic ellipticities of the cross polarizers, which are essential for obtaining accurate values. The optical system was applicable to simultaneously measure the linear dichroism (LD), circular dichroism (CD), linear birefringence (LB) and circular birefringence (CB) spectra of an intercalated compound in the ultraviolet and visible regions. We found the Kramers-Kronig relation between CB and CD as well as in the case of LB and LD. Changes in LB and LD signals as obtained from HAUP measurements originated from the molecular orientation of guest molecules by the intercalation. Moreover, CB and CD signals indicated the appearance of induced chirality in the intercalated azobenzene derivative compound. These results demonstrated the usefulness of the HAUP system for evaluating the molecular conformation of chiral anisotropic specimens.

:Crystal specimens of the γ-polymorph of achiral glycine which crystallize in space groups P3(1) and P3(2) as determined by the anomalous X-ray scattering method are shown to be laevorotatory and dextrorotatory, respectively, as determined by optical rotation of the crystals.

Crystal specimens of the gamma-polymorph of achiral glycine which crystallize in space groups P3(1) and P3(2) as determined by the anomalous X-ray scattering method are shown to be laevorotatory and dextrorotatory, respectively, as determined by optical rotation of the crystals.

The lamellar architecture found in many natural fibrous tissues has a significant bearing on their specific functions. However, current engineered tissues have simultaneously no realistic structures and no adequate functions. This study demonstrates a two-step process for obtaining structurally mimicking laminates in natural fibrous tissues with good optical and mechanical characters from purified-clinically-safe collagen molecules. Stacked lamella structures can be created by repeating flow casting, with the controlling parallel/orthogonal directionalities of each thin single-layer (2-5 mu m in thickness). The transparency of laminates is successfully improved by a unique multi-cyclic vitrification with chemical cross-linking. The directionalities of optical and mechanical functions in laminates are strongly related with the preferential collagen alignments in the laminates. The tensile strength of laminates is extremely higher than any other engineered materials as well as native cornea, which exhibit an orthogonal laminated collagen structure and a good optical transmission. (C) 2010 Elsevier Ltd. All rights reserved.

The lamellar architecture found in many natural fibrous tissues has a significant bearing on their specific functions. However, current engineered tissues have simultaneously no realistic structures and no adequate functions. This study demonstrates a two-step process for obtaining structurally mimicking laminates in natural fibrous tissues with good optical and mechanical characters from purified-clinically-safe collagen molecules. Stacked lamella structures can be created by repeating flow casting, with the controlling parallel/orthogonal directionalities of each thin single-layer (2-5 mu m in thickness). The transparency of laminates is successfully improved by a unique multi-cyclic vitrification with chemical cross-linking. The directionalities of optical and mechanical functions in laminates are strongly related with the preferential collagen alignments in the laminates. The tensile strength of laminates is extremely higher than any other engineered materials as well as native cornea, which exhibit an orthogonal laminated collagen structure and a good optical transmission. (C) 2010 Elsevier Ltd. All rights reserved.

Although polyethylene oxide (PEO) offers several advantages as a sieving polymer in SDS capillary polymer electrophoresis (SDS-CPE), solution properties of PEO cause deterioration in the electrophoresis because PEO in solution aggregates itself, degrades into smaller pieces, and forms polymer-micelle complexes with SDS. We examined protein separation on SDS-CPE with PEO as a sieving matrix in four individual buffer solutions: Tris-CHES, Tris-Gly, Tris-Tricine, and Tris-HCl buffers. The solution properties of PEO as a sieving matrix in those buffers were examined by dynamic light scattering (DLS) and by surface tension. Preferential SDS adsorption onto PEO disturbed protein-SDS complexation and impaired the protein separation efficiency. Substantial adsorption of SDS to PEO was particularly observed in Tris-Gly buffer. The Tris-CHES buffer prevented SDS from adsorbing onto the PEO. Only Tris-CHES buffer achieved separation of six proteins. This study demonstrated efficient protein separation on SDS-CPE with PEO.

SmCo5 alloy is a promising candidate for ultra-high-density perpendicular magnetic recording (PMR) media because of its high uniaxial magnetocrystalline anisotropy K-u of more than 1.1 x 10(8) erg/cm(3). Previously, we successfully achieved high K-u in a sputter-deposited SmCo5 thin film by introducing a Cu/Ti dual underlayer. However, in order to apply the SmCo5 films to practical PMR media, it is necessary to decrease medium noise. A granulated magnetic film comprising of small and magnetically decoupled grains is effective in reducing the medium noise. In this paper, we have proposed a new granular film that is fabricated by partial thermodiffusion of Cu between the Sm-Co continuous layer and the Cu underlayer, which is granulated using compositional segregation caused by the addition of Ta2O5. We have analyzed the magnetic properties, magnetic domain size, and magnetization reversal process of the proposed SmCo5 film. The magnetic domain size decreased and the magnetization reversal process changed from the magnetic-wall-motion mode to a coherent rotation mode to some extent on isolation of magnetic grains. The read/write characteristics of granulated SmCo5 double-layered media were also evaluated. The medium noise decreased and the signal-to-noise ratio increased for the granulated double-layered (PMR) medium. (C) 2010 Elsevier B.V. All rights reserved.

A Sm-Co-CrTa granular layer between a Sm-Co continuous layer and a Cu underlayer was prepared in order to improve magnetic properties and magnetic reversal process of Sm-Co perpendicular film. A phase of CrTa alloy in Sm-Co-CrTa layer has a role in control of Cu partial interlayer diffusion between the Sm-Co continuous layer and the Cu underlayer. The Cu diffusion provides the partial crystallization of SmCo5 in the continuous layer. Although the perpendicular coercivity of films decreased slightly by introducing the CrTa alloy into Sm-Co layer, the magnetic intergranular exchange interaction in the films was drastically improved. Size of average magnetic cluster became smaller and magnetization reversal process was changed from a wall-motion to a coherent rotation for increasing the thickness ratio of Sm-Co-CrTa/Sm-Co layers. We confirmed that an addition of Sm-Co-CrTa layer is effective to reduce the intergranular exchange interaction in Sm-Co perpendicular films without deterioration of perpendicular magnetic anisotropy.

This article discusses differences in physicochemical properties such as solubility and melting point between (S)-thalidomide and (RS)-thalidomide based on crystal structures determined by X-ray diffraction experiments. Investigation of such differences is of great importance because thalidomide has attracted considerable attention again due to its wide-range bioactivity for intractable diseases. In this article, structures of hydrogen-bonded rings were compared between asymmetric homochiral dimers in (S)-thalidomide crystal and symmetric heterochiral dimers in (RS)-thalidomide crystal. The heterochiral dimer was evaluated to be more stable than the homochiral dimer by the energy calculations for hydrogen-bonded rings in those dimers. These results indicate that differences in physicochemical properties between enantiomeric and racemic thalidomides originate from the difference of structural stability between homochiral and heterochiral dimers.

Stem cells nanotechnology has emerged as a new exciting area, and holds great potential for research and development of stem cells as novel therapeutic platforms for genetic, traumatic, and degenerative medicine. Vital to the success of this technology are approaches that reproducibly facilitate in vivo cell tracking, expansion, differentiation, and transplantation. Herein we reported the effects of CdSe/ZnS quantum dots covered multi-walled carbon nanotubes (FMNTs) on mice embryonic stem cell line CCE cells. The FMNTs were prepared by plasma surface treatment and characterized by high resolution transmission electron microscopy (HR-TEM), and incubated with murine ES CCE cells for 1 to 28 day.These ES cells were observed by confocal laser scanning microscopy, and were analyzed by real time reverse transcription-polymerase chain reaction (RTPCR), flow cytometry (FCM) and MTT method. Results showed that prepared FMNTs exhibited green fluorescent signal, could enter into ES cells in time-dependent means, more than 20 μg ml-1 FMNTs induced ES cells become smaller and smaller as the incubation time increased, and inhibited cell growth in dose-and time-dependent means, induced apoptosis of ES cells
conversely, 5 μg ml-1 FMNTs could markedly stimulate the expression of Sox1 and Hsp27, and inhibit expression of OCT4 in ES cells, FCM analysis showed that differentiation marker Flk-1 exhibited higher expression compared with control ES cells. In conclusion, high dose of FMNTs can inhibit proliferation of ES cells, low dose of FMNTs can improve the differentiation of ES cells, FMNTs can have potential applications in in vivo tracking, imaging and regulation of the proliferation and differentiation of ES cells. © 2010 D. Cui, et al.

This article discusses differences in physicochemical properties such as solubility and melting point between (S)-thalidomide and (RS)-thalidomide based on crystal structures determined by X-ray diffraction experiments. Investigation of such differences is of great importance because thalidomide has attracted considerable attention again due to its wide-range bioactivity for intractable diseases. In this article, structures of hydrogen-bonded rings were compared between asymmetric homochiral dimers in (S)-thalidomide crystal and symmetric heterochiral dimers in (RS)-thalidomide crystal. The heterochiral dimer was evaluated to be more stable than the homochiral dimer by the energy calculations for hydrogen-bonded rings in those dimers. These results indicate that differences in physicochemical properties between enantiomeric and racemic thalidomides originate from the difference of structural stability between homochiral and heterochiral dimers.

Carbon nanotubes'bio-effects have become a hotspot. In recent years, my group and collaborators try to use single walled carbon nanotubes(SWCNTs) as drug delivery system to regulate proliferation and differentiation of mouse stem cells. We observed that low dose of SWCNTs stimulate stem cells'proliferation and differentiation, higher dose of SWCNTs improve stem cells' apoptosis. Y-27632, a selective inhibitor of p160 Rho-associated coiled-coil kinase, can conjugate with SWCNTs and form the nanocomposites, which markedly inhibit the apoptosis of mouse stem cells, improve the proliferation and differentiation of stem cells. The potential mechanism of effects of Y-27632-SWCNT composites on stem cells is also dicussed. Our primary results suggest that special enzyme modified SWCNTs can be used to regulate proliferation and differentiation of stem cells, which has potential application in stem cells-based therapy. ©The Electrochemical Society.

A highly selective, ultrasensitive, fluorescence detection method for DNA and antigen based on self-assembly of multiwalled carbon nanotubes (CNTs) and CdSe quantum dots (QDs) via oligonucleotide hybridization is reported. Mercaptoalkyloligonucleotide molecules bind to the quantum dots, while amineoalkyloligonucleotides bind to CNTs with -COCl surface groups. QDs and CNTs further assemble into nanohybrids through DNA hybridization in the presence of target complementary oligonucleotides. The method is achieved with good repeatability with the detection limit of 0.2 pM DNA molecules and 0.01 nM antigen molecules. This novel detection system can also be used for multicomponent detection and antigen-antibody immunoreaction. The novel system has great potential in applications such as ultrasensitive pathogen DNA or antigen or antibody detection, molecular imaging, and photoelectrical biosensors.

An SmCo(5) alloy is a promising candidate for ultra-high density magnetic recording media because of its strong uniaxial magnetocrystalline anisotropy, whose constant, K(u), is more than 1.1 x 10(8) erg/cm(3). Recently, we successfully obtained high perpendicular magnetic anisotropy for a sputter-deposited SmCo(5) thin film by introducing a Cu/Ti dual underlayer. However, it is necessary to improve magnetic properties and read/write (R/W) characteristics for applying SmCo(5) thin films to perpendicular magnetic recording media. In this study, we focused on reduction of magnetic domain size and change of a magnetization reversal process of SmCo(5) perpendicular magnetic thin. films by introducing carbon (C) atoms into the constituent Cu underlayer. The magnetic domain size became small and the ratio of coercivity (H(c)) against magnetic anisotropy (H(k)) which is an index of the magnetization reversal process was increased by adding C atoms. We also evaluated the R/W characteristics of SmCo(5) double-layered media including C atoms. The medium noise was decreased and signal-to-noise ratio increased by introducing the C. The addition of C into the Cu underlayer is effective for changing the magnetization reversal process, reducing medium noise and increasing SNR. (C) 2008 Published by Elsevier B. V.

Magnetic circular dichroism (MCD) and X-ray absorption spectra (XAS) at the Co L(2,3)-edge of [Co/Pd](20) and [CoB/Pd](20) multilayered films, which were fabricated at 260 degrees C with different magnetic layer thicknesses (delta), have been measured. The lineshapes of XAS-MCD show that the electronic state of Co 3d of the films hardly changes even when sputtered at higher temperatures. The expectation values of orbital and spin angular momentum (< L(z)> and < S(z)>) are estimated using the sum rule, and it is found that < L(z)>/< S(z)> in delta<0.5 nm is larger than that in delta>0.5 nm. (C) 2008 Elsevier B. V. All rights reserved.

An extremely enhanced enantioselectivity was achieved for the detection of enantiomers of alanine (Ala), leucine (Leu), and 3,4-dihydroxyphenylalanine (DOPA) based on the voltammograms for the deposition of Cu from Cu complexes of the amino acids at an Au electrode modified with a self-assembled monolayer (SAM) Of L-homocysteine (Hcy). The enantioselective current density peak for the Cu deposition was found to change with increasing number of potential cycles after the addition of Cu(II), and the highest enantioselectivity was observed immediately after the addition of Cu(II). Besides, enantio selectivity was not observed with proline, whose five-membered ring contains the nitrogen atom of a secondary amino group, while some amino acids with a primary amine group such as Ala, Leu, and DOPA exhibited enantioselectivity. These results suggest that the chiral ligand exchange reaction at the L-Hcy SAM-modified Au electrode, namely, the enantioselective formation of diastereomeric complexes of Cu(II) with target enantiomers and L-Hcy self-assembled on the Au electrode, plays an important role in the chiral discrimination based on the Cu deposition. (c) 2006 Elsevier B.V. All rights reserved.

Sputter-deposited SmCos thin films exhibiting high perpendicular magnetic anisotropy were studied for materializing ultra high density magnetic recording. This study put emphasis on the fabrication of SmCos double-layered perpendicular magnetic recording media. A double-layered medium with a Ru buffer layer introduced between a Cu/Ti intermediate layer and a Co-Zr-Nb soft magnetic underlayer exhibited high perpendicular magnetic anisotropy, whereas that without the Ru buffer layer did not. Auger electron spectroscopy revealed that the Ru buffer layer inhibited unfavorable interdiffusion between the Cu/Ti intermediate layer and the Co-Zr-Nb soft magnetic underlayer. In addition, the readwrite characteristics of the SmCos double-layered perpendicular magnetic recording media were evaluated for the first time. copyright The Electrochemical Society.

The soft x-ray absorption and magnetic circular dichroism spectra at the Co L-2,L-3-edges of [Co/Pd](20) and [CoB/Pd](20) multilayered films, which were sputter- deposited in Ar gas containing N-2 at room temperature, were measured to investigate the electronic and spin states of the films. The macroscopic magnetic properties, such as coercivity and saturation magnetization, and microstructural properties, such as grain size and preferred orientation, were markedly changed for the [Co/Pd](20) film by the B doping and N-2 addition. The B doping and/or the addition of N-2 gas caused appreciable changes not only in macroscopic magnetic properties but also in microscopic properties, such as the spin angular momentum and orbital angular momentum, throughout the multilayered film. On the other hand, a new spectral feature at the high energy side of the Co L-3-edge peak in x-ray absorption spectra was found in only the films with N-2 added. Thus, the microscopic properties, such as electronic and spin states, of the Co 3d electronic state for the [Co/Pd](20) and [CoB/Pd](20) films were changed by only the sputtering process with additive N-2 gas.

Effects of the Cu underlayer thickness and the addition Of Cu to a Sm-Co layer on magnetic properties and microstructure Of SmCo5 thin films exhibiting perpendicular magnetic anisotropy were studied. The origin of the perpendicular magnetic anisotropy was discussed from these experimental results. A thick Cu underlayer of more than 100 nm brought about high perpendicular magnetic anisotropy leading to the squareness ratio equal to unity. The Cu addition enhanced the perpendicular magnetic anisotropy and reduced the Cu underlayer thickness required to obtain the squareness ratio of unity. X-ray diffractometry showed that the crystalline orientation of the Sm-Co layer did not correlate with that of the Cu underlayer. Auger electron spectroscopy revealed that Cu atoms were diffused up to the Sm-Co layer from the Cu underlayer. From the results, Cu atoms existing in the Sm-Co layer were suggested to be strongly related with an appearance of the perpendicular magnetic anisotropy by introducing the Cu underlayer. (c) 2005 Elsevier B.V. All rights reserved.

The effect of the surface morphology of gold-deposited quartz substrate on the enantioselective crystallization of leucine was investigated by using quartz crystal microbalance (QCM) and X-ray diffraction methods. The gold substrate was modified with a self-assembled monolayer with covalently attached D-leucine molecules. For a rough surface with root-mean-square (RMS) roughness of 17 nm, the QCM measurement showed a continuous decrease in frequency, while for a smooth surface with RMS roughness of 2 nm, essentially no change in frequency was observed. Nevertheless, leucine crystals with high crystallinity were clearly formed on the smooth surface.

X-ray absorption and magnetic circular dichroism spectra (XAS-MCD) of the Dy M-4,M-5-edges of DyxCo100-x (x=15-33) thin films are measured. The advantage of element and orbital selectivity in the XAS-MCD measurements enables us to directly observe the magnetic moments of specified elements. The MCD intensity at the Dy M-5-edge is maximum when the incident X-ray is normal to the surface and the incident angle dependence of the MCD intensity shows a sine curve. That gives us information about the angular distribution of the Dy magnetic moments with respect to the total magnetization direction and the opening angle of the cone. Applying the sum rule, the expectation value of orbital magnetic moment was estimated. The half opening angle of the random distribution of the moments were estimated and it was found that the angle has its minimum value around x=20. (c) 2005 Elsevier B.V. All rights reserved.

An investigation was carried out on the effects of the addition of Cu and the thickness of the SmCo5-based thin film with perpendicular magnetic anisotropy upon its magnetic properties, with the aim of reducing the Cu/Ti underlayer thickness. As a result, the Cu/Ti underlayer thickness necessary to obtain the squareness ratio of unity was successfully reduced from 125 to 50 nm. Moreover, for the SmCo5 double-layered perpendicular magnetic recording media with a CoZrNb soft magnetic underlayer, the Cu/Ti underlayer thickness was further reduced to 35 nm. However, the magnetic cluster size and the values of coercivity and saturation field of the SmCo5 media were found to be too large. Thus, we recognized the need for adjusting the cluster size and the magnetic properties to appropriate values, and also the need for investigating the possibility of using this material as patterned media or thermally assisted recording media.

Effects of the Pd seeds formed by an electrochemical process on the microstructures of Co/Pd multilayered perpendicular recording media were investigated. By immersing a CoZrNb soft magnetic underlayer (SUL) into PdCl2 aqueous solution, island-like Pd clusters were deposited on the SUL, resulting from the electrochemical substitution reaction. Transmission electron microscopic observations revealed that the columnar Co/Pd multilayered grains with clear boundaries grew on the SUL with the Pd clusters. The clear grain boundaries, where the densities of Co and Pd elements were low, were thought to cause the magnetic exchange decoupling between the Co/Pd grains, leading to an increase of perpendicular coercivity and a decrease of magnetic cluster size of Co/Pd multilayered film. Consequently, lower medium noise was obtained for the Co/Pd multilayered medium with the Pd clusters than for that with a sputter-deposited Pd seedlayer. From these investigations, it was clarified that the SUL surface with Pd clusters provided the effective nucleation sites for a well-defined Co/Pd multilayered grain growth. (C) 2004 Elsevier B.V. All rights reserved.

SmCo5 thin films with Cu seedlayer exhibiting perpendicular magnetic anisotropy were studied. The perpendicular magnetic anisotropy was enhanced using the Sm-Co layer formed by laminating Co and Sm sub-layers alternately. The Co/Sm laminate structure promoted the crystallization Of SmCo5 and the preferred orientation of its c-axis. The perpendicular magnetic anisotropy was further improved by suppressing the surface roughness of the Cu seedlayer. The SmCo5 thin film prepared in this study possesses an adequate corrosion resistance when judged by an electrochemical analysis. (C) 2004 Elsevier B.V. All rights reserved.

A novel fabrication process of a soft magnetic underlayer (SUL) for a double-layered perpendicular magnetic recording medium was presented. The CoNiFeB SUL was deposited on a silicon disk substrate using an electroless deposition. The Ni seed layer for the electroless deposition was prepared by an electrochemical process. The surface of the deposited SUL was subjected to a chemical mechanical polishing to be flattened, and R-a value of the SUL was less than 0.4 nm. A magnetic domain structure greatly depended on the electroless deposition condition. Particularly, the control of an agitation speed during electroless deposition is much effective for the suppression of distinct domain walls appearing in CoNiFeB underlayers. (C) 2004 Published by Elsevier B.V.

Effects of N-2 additive gas and/or substrate heating during the sputtering of [CoB/Pd](20) multilayered films on the magnetic properties and microstructure were investigated. The [CoB/Pd](20) film fabricated at 20degreesC by adding N-2 gas during sputtering possessed the finest grain size and the smallest magnetic cluster size among media fabricated in this study although the film sputter-deposited at 260 degreesC by adding N-2 gas exhibited the weakest intergranular exchange coupling. It was revealed that the double-layered perpendicular magnetic recording medium that consisted of the [CoB/Pd](20) film fabricated at 20degreesC by adding N-2 gas exhibited the highest signal-to-noise ratio in the read write characteristics. (C) 2004 Elsevier B.V. All rights reserved.

Thin films of SmCo5 with extraordinarily high perpendicular magnetic anisotropy were prepared by introducing a Cu/Ti dual underlayer and controlling the substrate temperature during the sputter deposition. Under optimized conditions, the magnetic anisotropy constant reached 4.0x10(7) erg/cm(3), and the coercivity and the remanence ratio in the direction perpendicular to the film surface were 12.0 kOe and unity, respectively. The high perpendicular magnetic anisotropy is attributed to the high degree of preferred orientation of the c axis; the full width at half maximum in the rocking curve of SmCo5(002) reflection was 3.1degrees. (C) 2004 American Institute of Physics.

Pd cluster seeds for a double-layered perpendicular magnetic recording medium composed of a Co/Pd multilayered film and a CoZrNb soft magnetic underlayer (SUL) were fabricated with an electrochemical treatment. By immersing the SUL into an aqueous PdCl2 solution, the substitution of Pd for Co at the surface of the SUL took place, which was caused by the difference in electrochemical redox potential between Pd and Co. Uniformly distributed Pd clusters with 8 nm in diameter were successfully formed with the treatment for the optimized duration. Use of the Pd clusters as the seeds for deposition of the Co/Pd multilayered film increased the perpendicular coercivity and reduced the size of magnetic cluster of the film. These results suggested that the Pd cluster seeds led to the formation of magnetically isolated Co/Pd multilayered grains, improving the magnetic properties of Co/Pd multilayered film.

The electronic and spin states of [Co/Pd] multilayered perpendicular magnetization films with various seedlayers have been investigated by means of soft x-ray absorption and magnetic circular dichroism spectroscopy at the Co L-2,L-3-edges. The expectation values of the orbital angular momentum <L-z> and the spin angular momentum <S-z> of Co atom in the [Co/Pd] multilayered film were estimated using the sum rule. It was found that the seedlayer changes macroscopic magnetic properties of the [Co/Pd] multilayered film without affecting the electronic and spin states of the upper layers of Co. (C) 2004 American Institute of Physics.

A 10 nm Pd/Si dual thin film was developed as a seed layer for a Co/Pd multilayer in double-layered perpendicular magnetic recording media. The Pd/Si seed layer, sputter deposited under Ar sputtering gas containing N-2 and postannealed at 400 degreesC, markedly reduced intergranular exchange coupling of the Co/Pd multilayered film, resulting in a decrease in both the slope parameter, defined as 4pi(dM/dH)(H=Hc), and the magnetic cluster size. Consequently, medium noise was essentially reduced, thereby improving the signal-to-noise ratio of the Co/Pd recording media on a CoZrNb soft magnetic underlayer. The addition of N-2 gas effectively decreased the grain size of Pd in the seed layer. A Pd/Si seed layer prepared with both processes exhibited a granular structure of fine Pd-rich grains surrounded by a Si-rich amorphous region, which provided nucleation sites for the growth of well-separated Co/Pd multilayered grains. (C) 2004 American Institute of Physics.

Microstructure and magnetic properties of sputter deposited Co/Pd multilayered perpendicular magnetization films with amorphous C or Si seedlayer were investigated. The angstrom scale surface roughness of the seedlayer causes fine crystal grains to form in the Co/Pd multilayer and to decrease the extent of intergranular exchange coupling, while it obstructs the formation of a regular interface between Co and Pd layers. The Si seedlayer, which exhibits a surface roughness lower than the C seedlayer, yields Co/Pd multilayered films with the lowest intergranular exchange coupling and the highest coercivity. The improvement in magnetic properties of the Co/Pd film with Si seedlayer is attributable mainly to the formation of Pd2Si at the interface between the Co/Pd layer and the Si seedlayer. The Pd2Si provides suitable nucleation sites for the grain growth of Co/Pd multilayered film that can be utilized as a perpendicular magnetic recording medium. (C) 2002 American Institute of Physics.

Effects of the introduction of a Pd/Si dual seedlayer on the microcrystalline structure and magnetic properties of [Co/Pd](n) multilayered perpendicular magnetic recording media were investigated. The Pd/Si dual seedlayer was composed of a Pd upper seedlayer and a Si under seedlayer. The Pd upper seedlayer with a thickness of up to 10 nm markedly increased the coercivity of [Co/Pd](n) multilayered media in the direction perpendicular to the film surface. The highest coercivity of 7.8kOe was obtained for the [Co/Pd](10) medium with a Pd (10nm)/Si (100nm) dual seedlayer. The Pd upper seedlayer not only facilitated the formation of regular interfaces between the Co and Pd layers, but also reduced the thickness of the deteriorated initial layer in the [Co/Pd](n) multilayer, resulting in enhancement of the magnetic anisotropy field. The [Co/Pd](n) multilayered medium with the Pd/Si dual seedlayer exhibited weak intergranular exchange coupling between [Co/Pd](n) grains, which led to excellent read-write characteristics. (C) 2002 Elsevier Science B.V. All rights reserved.

The relationship between crystallographic grain orientation and the three kinds of surface energy components; dispersion, polar, and hydrogen bonding components, in Co73Cr18Pt6Ta3 perpendicular magnetic recording media with an amorphous C or a Ti90Cr10 underlayer was discussed. Each surface energy component of the thin film was calculated from an extended Fowkes theory by measuring the contact angle of a test liquid on the thin film. The experimental results revealed that the polar component of surface energy of the Co73Cr18Pt6Ta3 magnetization film with the C underlayer affected greatly the Co [001] preferred orientation of the Co73Cr18Pt6Ta3 magnetization film, while the surface energy of the Co73Cr18Pt6Ta3 magnetic layer with the Ti90Cr10 underlayer had little influence on the distribution of it. (C) 2001 Elsevier Science B.V. All rights reserved.

Signal and noise characteristics of Co/Pd multilayer perpendicular magnetic recording media are discussed based upon MFM analysis. The noise of the Co/Pd multilayer media is originated mainly from irregularities in the magnetic transition regions, and can be drastically suppressed by increasing the thickness of the carbon underlayer although a large number of reversed magnetic domains between the magnetic transitions still exist. The fine magnetic clusters formed in the medium with a thick carbon underlayer result in clear magnetic transition boundaries of recorded bits in the high recording density region. By examining the profile of the M-H loops. the decrement in the x value, which is defined as the slope of M-H loop at the value of coercivity, improves the signal to noise (S/N) ratio for the Co/Pd multilayer media. (C) 2001 Elsevier Science B.V. All rights reserved.

The effect of amorphous carbon underlayer thickness on the microstructure of the CO/Pd multilayer perpendicular magnetic recording media was investigated. From the magnetic force microscopy observation in the AC-demagnetized state of the Co/Pd multilayer media, the magnetic cluster size was observed to effectively decrease with an increase in carbon underlayer thickness, where the higher coercivity and the higher SIN ratio of the Co/Pd multilayer media were obtained with the thicker underlayer. Furthermore, the distribution of [111] orientation of FCC-Pd became broader, and the grain size decreased with an increase in the carbon underlayer thickness. These effects caused the magnetic exchange decoupling of Co/Pd multilayer media. We suggested that the change of microstructure was directly related to the surface roughness of the amorphous carbon underlayer. (C) 2001 Elsevier Science B.V. All rights reserved.

Cinchona-alkaloid/Selectfluor combinations efficiently fluorinate a variety of carbonyl compounds in a highly enantioselective manner to furnish chiral alpha -fluorocarbonyl compounds. The DHQB/Selectfluor combination is effective for the enantioselective fluorination of indanones and tetralones 1 in up to 91% ee. The first enantioselective syntheses of chiral derivatizing reagents 3 was accomplished with high ee and in high chemical yields by the DHQDA/Selectfluor combination. 3-Fluorooxindoles 7 were prepared with ee up to 83% using the (DHQ)zAQN/Selectfluor or the (DHQD)(2)PYR/Selectftuor combination. Since the combinations are conveniently prepared in situ from readily available reagents, the present system represents a practical method for enantioselective fluorination. X-ray crystallography and H-1 NMR analyses of the cinchona alkaloids/Selectfluor combination have established that the species that mediate this novel reaction are N-fluoroammonium cinchona alkaloid tetrafluoroborates, which adopt open conformations.

The effect of amorphous carbon underlayers on magnetic properties and read-write characteristics of Co73Cr18Pt6Ta3 single layer and Co/Pd multilayer perpendicular magnetic recording media were investigated. The increase in H-c and decrease in alpha, defined as 4 pi (dM/dH)(H=Hc), were observed by increasing the underlayer thickness for both Co-73 Cr18Pt6Ta3 and Co/Pd media. The media with a low alpha value, suggesting a decrease in the exchange coupling, exhibited the higher coercivity and the improvement of S/N ratio. In read-write experiments, the improvement of S/N ratio for the Co/Pd media was achieved up to 400 kFRPI or even higher in the recording density by increasing carbon underlayer thickness, while that for the Co73Cr18Pt6Ta3 media was obtained up to ca. 250 kFRPI.

Sputter-deposited amorphous carbon was applied as an underlayer for a Co73Cr18Pt6Ta3 Single layer perpendicular magnetic recording medium. It is shown that the amorphous carbon underlayer can control the Co [001] preferred orientation of the Co73Cr18Pt6Ta3 magnetic recording layer and that the microcrystalline structure, magnetic properties, and read-write characteristics of Co73Cr18Pt6Ta3 media are greatly dependent on the carbon underlayer thickness. By x-ray diffraction experiments and transmission electron microscopy observations, it was confirmed that the distribution of the c-axis orientation of Co grains becomes broader in the direction perpendicular to the film surface with increasing carbon underlayer thickness. Furthermore, the Co73Cr18Pt6Ta3 medium with a thick carbon underlayer indicated a relatively high perpendicular coercivity of 2800 Oe and an excellent signal to noise ratio in read-write characteristics. (C) 2000 American Institute of Physics. [S0021-8979(00)03324-7].

The influence of substrates on magnetic property and crystalline orientation of CoCrTa/TiCr perpendicular magnetic recording medium was investigated using a glass plate and a Si(1 0 0) single crystal. Magnetic measurements revealed that the film sputtered on a Si(1 0 0) substrate possessed a higher perpendicular coercive force than that on glass, where the pretreatment of the Si(1 0 0) substrate by aqueous HF solution effectively improved the magnetic properties. X-ray diffraction analysis of the films indicated that the crystallinity of the TiCr layer formed on the Si(1 0 0) substrate with the HF pretreatment was higher than that on the glass substrate. It was also found that CoCrTa and TiCr layers on the Si(1 0 0) substrate with the KF pretreatment had a narrower distribution of their c-axis orientation than those on glass substrate. The results of X-ray diffraction analysis were consistent with those of the TEM observation for cross-section bright- and dark-field images and the corresponding THEED patterns. These results suggest that the crystalline surface of the Si(1 0 0) substrate with HF pretreatment has the effect of inducing preferred orientation in the TiCr underlayer, which leads to a decrease in distribution of the c-axis orientation of Co grains in the CoCrTa layer, resulting in an increase in the perpendicular coercive force. (C) 2000 Elsevier Science B.V. All rights reserved.

The components of the gyration tensor of the enzyme lysozyme were measured by using the HAUP method: g(11) = - 0.90 x 10(-5) and g(33) = 1.05 x 10(-5) at 303.4 K and a wavelength of 4880 Angstrom. The optical rotatory powers along the a and c axes in the same conditions were calculated: rho(a) = -21.3 and rho(c) = -24.8 degrees cm(-1). The optically active property of lysozyme is strange in that, although it contains a considerable quantity of alpha-helices (about 30%), the rotatory powers are unexpectedly small in magnitude, one order of magnitude less than those of quartz and with very large anisotropy. A conceptual consideration of this phenomenon is given. In order to assess the difference between the structures in both crystalline and solution states, the chirality index r was calculated to be 0.16. This value indicates that the structural change of lysozyme from the solution into the crystalline state is expressed by an increase of 19% in optical activity. From the NMR results [Smith et al. (1993), J. Mol. Biol. 229, 930-944], it is anticipated that the r value reflects the increased constraint in atomic motion in the side chains of exposed amino acid residues in the crystalline state.

Optical gyration G, birefringence Delta n and their electric-field E dependences of transparent ceramics of Pb0.92La0.08(Zr-0.65 Ti-0.35)(0.98)O-3 were studied by using high accuracy universal polarimeter (HAUP) in a temperature range between 10 degrees C and 130 degrees C. The high-temperature phase manifested neither spontaneous nor induced G, while the low-temperature phase did characteristic hysteresis loops of G and Delta n with respect to E. Group-theoretical consideration of gyro-optical properties of both phases led us to the conclusion that the high-End low-temperature phases are cubic T-h and trigonal C-3, the same as found in Pb0.92La0.08(Zr0.70Ti0.30)(0.98)O-3 ceramics. The free energy function of both phases was determined by using these electro-optic effects. It is found that both ceramics undergo the same phase transition and manifest similar dielectric and optical properties.

In a project of revealing gyro-optical properties of amino acids that build up proteins, all the components of the gyration tensor and the birefringence of L-aspartic acid have been successfully measured as a function of temperature although the crystal belongs to the mono-clinic system. The temperature dependence of the rotation of the gyration surface around the crystal lographic b axis was also clarified. It is of interest that the chirality index of this crystal was found to be almost the same as that of glutamic acid, another amino acid.

Temperature dependences of thermal strains of superconducting Bi2Sr2CaCu2O8 were measured by using the two-dimensional reciprocal-lattice method of x-ray diffraction in the temperature range between 15 and 300 K. Accuracies of measuring the lattice strains attained 1.6 x 10(-6). Very small anomalies of the lattice constants and lattice volume took place at T-c of the transition point. They were caused by definite discontinuities of the thermal-expansion coefficients. Using previously reported values of specific heat and isotropic compressibility a nearly temperature-independent equivalent Gruneisen parameter gamma(T) was derived as 0.89 +/- 0.11. From the extrapolation of the lattice volume of the high-temperature phase into the superconducting temperature region, additive lattice strains were found to appear spontaneously in the superconducting phase. From this fact it was concluded that a structural phase transition of the second order took place with the onset of superconductivity.

It has been known that oxo amide crystals made up of achiral molecules can be photochemically converted into optically active beta-lactams by irradiation with a high pressure mercury lamp. Although the oxo amide crystal belongs to an enantiomorphic class D-2, its optical activity could not be detected so far. We successfully measured the components of the gyration tensor of the oxo amide crystal by using the HAUP (high accuracy universal polarimeter) method: g(11) = -3.5 x 10(-4) (-79 degrees/mm), g(22) = -1.4 x 10(-4) (-32 degrees/mm), g(33) = -3.0 x 10(-4) (-68 degrees/mm) at 305 K, where the optical rotatory powers are indicated in parentheses. It has been proved by direct experiments that the optical activity of the reactant and the product in this reaction system remains unchanged over the photocyclization process.

As the first study on gyro-optical properties of amino acids, temperature dependences of the gyration tensor components of L- and D-glutamic acids were measured by using the HAUP (high-accuracy universal polarimeter). It was confirmed that the corresponding tensor components of the two enantiomers are the same in magnitude but opposite in sign. It is proposed that r = (rho(C)(0) - rho(S)(0))/rho(C)(0) be defined as the 'chirality index', where rho(C)(0) and rho(S)(0) designate rotatory powers per molecule in a crystal and in a dissolved state in liquid, respectively. It represents a measure of structural contribution of optical activity (OA) in a crystal. This value is 0.992 in glutamic acids.

A fundamental optical study was performed on superconducting Bi2Sr2CaCU2O8 by Using a high-accuracy universal polarimeter (HAUP). As this crystal is strongly linearly dichroic, we developed the extended HAUP theory which includes the treatments of the optical dichroisms. After having determined the optical nature of the crystal, we applied the extended HAUP method to a thin (001) plate specimen with light traveling to the front and rear directions in the specimen. These two experiments permitted us to separate the reciprocal and nonreciprocal optical effects. No sign of the nonreciprocal effects was found in the HAUP transmission experiment. A gyration tensor component g(33) takes place suddenly at T-c (90 K), increases with decreasing temperature, and reaches 1.87X10(-4) (36 degrees/mm of rotatory power) at 15 K. A steep change of birefringence hn with temperature also occurs below T-c. From the behaviors of g(33) and Delta n with temperature, it can be concluded that the crystal undergoes a second-order phase transition at T-c into an optically active class. The crystal manifests large linear dichroism, i.e., Delta m=-2.2X10(-2).

Temperature and biasing electric field dependences of a gyration tensor component g(12) of ammoniumu sulfate were measured by using the high accuracy universal polarimeter, HAUP, together with birefringences. g(12) was found to appear abruptly at the Curie point and to keep the constant value irrespective of change of the temperature. The x-rays two-dimensional method was applied for measuring the lattice strains from 300K down to 6K.

The symmetry changes of the gyration tensor components of the solid polymers with a spiral orientation am clarified with respect to the changes of the density distribution function of the constituent crystallites. Any constituent crystals of optically active polymers should be regarded as uniaxial and enantiomorphic as far as the gyration is concerned. When the density distribution becomes perfectly homogeneous in the three-dimensional space, the gyration tensor components are reduced to a single component, (8)over bar>. Two rotatory powers of poly-L-lactic acid are compared; one is calculated from measured values in the solid state, the other is a measured value in chloroform solution by Goodman and D'Alagni. It is striking that the former is 10(3) times larger than the latter. This means that the helical conformations of the residues which clearly exist in the solid state are destroyed in the liquid solution.

The methods of measuring optical activity of solid polymers are reviewed. The extreme difficulty of the methods is exhibited in serious drawbacks of the traditional statistical methods. The invention of HA UP (high accuracy universal polarimeter) method by Kobayashi et al has opened a way to perfect measurements of gyro-optical properties of any solids. As an example of application of the HAUP method to helical polymers, the process of analyzing the gyration tensor components of poly-L-lactic acid and poly-D-lactic acid is illustrated in details. © 1995, Taylor &amp
Francis Group, LLC. All rights reserved.

Electric field dependences of optical activity and birefringence of Pb0.92La0.08(Zr0.7Ti0.3)(0.98)O-3(PLZT(8/70/30)) were studied using the high-accuracy universal polarimeter (HAUP) method in a temperature region between 0 degrees C and 90 degrees C. PLZT(8/70/30) was optically active in the low-temperature and inactive in the high-temperature phases. Furthermore it was revealed that gyration and birefringence in the low-temperature phase manifested typical butterfly hysteresis loops with respect to electric fields. From analysis of Weissenberg photographs, the ceramics of both high- and low-temperature phases were found to consist of crystallites which were distributed in equal weight along the total solid angles. Using the combined evidence from HAUP and X-ray methods, it was clarified that the classes of the high- and low-temperature phases are T-h and C-3, respectively.

Optical properties of PLZT(8/70/30) in various phases were studied by using HAUP method. Ferroelectric phase was found to be optically, active. From this result, it was revealed that the point group of PLZT should be C3 in the rhombohedral system(ferroelectric phase). Peculiar electric field dependences of gyration and birefringence in the intermediate phase were found. © 1994, Taylor &amp
Francis Group, LLC. All rights reserved.

Temperature dependences of gyration tensor component g11 and birefringence An of Gd2(MoO4)3 were measured at various wavelength by using high accuracy universal Polarimeter (HAUP). Spontaneous values of gn and An in the ferroelectric phase increased with decreasing temperature, but quadratic relations with respect to spontaneous polarization did not hold. The spontaneous Ans showed an anomalous peak at a wavelength of 334.7nm. Such a phenomenon has not been reported to date in any ferroelectrics. © 1994, Taylor &amp
Francis Group, LLC. All rights reserved.

Optical activity of a helical polymer, poly-L-lactic acid, was studied by using x-rays and HAUP methods. Gyrations depend considerably on the drawing actions. From the relation between gyrations and drawing ratios, the gyration tensor components are determined as g(1)=(-2.7 +/- 0.5) x10(-4) and g(3)=(8.3 +/- 0.2) x 10(-2). It is striking that a helical polymer like this material produces huge gyration along the helical chain.

Optical properties of La-modified lead zirconate titanate (9/65/35) in the intermediate phase were studied by the HAUP (high accuracy universal polarimeter) method. It was found that this material is optically inactive under electric fields. On the other hand, temperature dependence of the quadratic electrooptic coefficient was measured after careful corrections using the HAUP method.

Optical properties of pyroelectric and antiferromagnetic BaMnF4 were studied by using a high-accuracy universal polarimeter in the temperature range including the incommensurate phase transition point T(i). Both phases above and below T(i) were found to be optically active. The active gyration tensor components g(ij) were consistent with the reported symmetry of the crystal, i.e., C2-upsilon and C2 above and below T(i). Temperature dependences of all the gyration components were measured. It is striking that g23, which exists commonly in both phases, manifested itself a sharp peak at T(i). This divergence of g23 makes the transition perfectly second order. g11 along the incommensurate a axis develops conspicuously. The present results of the birefringences did not perfectly agree with previous reports: Although the temperature dependence of DELTA-n(c) coincided with the result of Schafer et al., those of DELTA-n(a) and DELTA-n(b) were quite different in their report. Rotation of the indicatrix takes place only around the a axis of the low-temperature phase. This fact confirms the validity of the point group C2 of the low-temperature phase. The rotation angle of the indicatrix was found to be one order of magnitude larger than that of the crystallographic axes. The rotation angle of the gyration surface was also evaluated. It is approximately two orders of magnitude larger than the rotation angle of the indicatrix. This fact clearly indicates that gyrations are very sensitively affected by the change of the order parameter.

Simultaneous measurements of the gyration, birefringence, and rotation angle of the optical indicatrix of Rochelle salt were successfully performed by using high-accuracy universal polarimetry. The three phases of the crystal were found to be optically active. It was revealed that the origin of ferroelectricity of the crystal is directly responsible for the occurrence of the optical activity. Birefringence in the ferroelectric phase cannot be explained by the usual electro-optic effect. Two possibilities are considered for this discrepancy.

1.記録機構,記録再生特性解析解法:
垂直記録単層膜媒体(軟磁性層のない媒体)の記録再生特性解析解法を構築した.[軟磁性層]-[記録層]-[ヘッド]の多重静磁気相互作用を取り入れた垂直記録二層媒体の再生特性,反磁界の解析解法は平成12-13年度に構築している.これらの手法が3項の実験結果の会席に用いられた.
2.媒体ノイズの解析解法:
平成14年に交流消磁ノイズ,直流磁化ノイズの解析解法を,平成15年に信号記録時のノイズ(変調ノイズ)のモデル化とノイズ解析解法を検討し,ノイズの実験結果からノイズ源の分離推定を可能にする手法を構築した.この理論,手法を[Co/Pd]n人工格子媒体の実験結果に適用し,ノイズ源の分離を行った.
3.ナノ構造人工格子・複合膜媒体の作製,微細構造,磁化機構,記録再生特性,ノイズ特性の解明:
(1).垂直記録二層媒体用極薄Pd/Siシード層の開発:平成12年に提案し,成功した『[Co/Pd]n人工格子垂直磁化層(記録層)下部にC, Siシード層を導入することにより記録層を高密度記録媒体に適した物理性質(磁化回転型磁化反転機構,磁性粒間の磁気交換結合の低減,微細な磁区)に改質する手法』を発展させ,[Co/Pd]n層/シード層/軟磁性層の系における極薄Pd/Siシード層を開発した.
(2).微細構造,磁化機構,記録再生特性:スパッタ法によるシード層形成時の窒素ガス導入,ポストアニール,PdとSiの膜厚比の検討により,高垂直磁気異方性,磁性粒間の低交換結合を維持したままPd/Si総厚を平成14年に10nm,平成15年に5nm(Pd(4nm)/Si(1nm))まで低減することに成功し,高記録分解能,高S/Nが得られた.これはシード層によるCo/Pd結晶粒の孤立化の促進と,シード層厚低減による[軟磁性層]-[記録層]-[ヘッド]の多重静磁気相互作用の増大の効果(1項)が寄与している.

1.ヘッド磁界分布解析法:記録再生過程の解析にとって必要なヘッド磁界分布の陽関数解析解法(積分方程式/Fourier解析法)を構築した.これらの手法はリングヘッド,MRヘッドなど各種ヘッドに適用できる.これらの結果が2項,3項に導入された.
2.垂直記録の記録再生過程解析解法:1項の解法を基に垂直記録(単層媒体系,2層媒体系)に対するリングヘッド及びMRヘッドの再生特性を解析し,記録再生特性が媒体/ヘッド系の主要パラメータの関数として具体的に定式化され,記録再生特性が記録系と再生系に分離して定量的に評価できるようになった.またこれらの結果は3項の媒体ノイズスペクトル解析にも適用された.
3.媒体ノイズ理論とノイズ源の定量的分離法:媒体ノイズのモデル化とノイズスペクトルを定式化し,磁気クラスターの大きさなどとノイズスペクトルの関係を定量的に明らかにした.またMFM(磁気力顕微鏡)による媒体の微視的磁化状態の実験的解析法を検討し,同手法を定量化した.
4.媒体の材料設計:2項,3項の検討結果から従来のCoCr系媒体よりも大きな磁気異方性を有する媒体が超高密度記録(200Gb/inch^2以上)では必要であることが明らかになった.アモルファスC下地層の上にCo/Pd人工格子膜を形成した複合垂直磁化膜媒体が非常に大きな磁気異方性をもちながら同時に磁化反転機構がCoCr系と同様な磁化回転型となり,記録の高分解能と低ノイズ特性を示すことを見出した.これはこのような新概念のナノ構造人工格子膜媒体が応用面ばかりでなく,磁化機構・記録機構の解明という磁性物理・磁性材料工学の観点からの新しい研究領域への発展を意味する.今後このような新概念媒体の磁化機構・記録機構の解明と同媒体による記録再生系の設計理論,設計手法の構築に発展させたい.

近年、1細胞レベルで分析するための要素技術の開発が行われている。レーザーや電気化学的な力を利用した技術が報告されているが、大型の装置を必要とするため、他の手法の開発も待望されている。本研究では、磁気誘導による1細胞トラップ技術を開発することを目的としている。磁性体をアレイ化した磁気マイクロアレイを作製し、抗体をアセンブルした磁気ナノ粒子を用いることで、磁気誘導によりターゲット細胞をトラップする。本細胞トラップ技術により作製された細胞アレイは、細胞間シグナル伝達物質解析における有用なツールとなることが予測され、創薬領域に大きく貢献すると期待される。シリコン基板上のマイクロサイズのホールアレイに無電解めっき法により、CoNiFe面内軟磁性体を導入し、磁気マイクロアレイを作製した。また、細胞の磁性化として、磁性細菌により合成されたProtein A発現磁気ナノ粒子を用いた。Raji細胞(B cell line)にマウス由来抗CD19抗体を導入した後、抗マウスIgG抗体固定化磁気ナノ粒子を導入し、細胞への磁性化を行った。この磁性化細胞を3種類の磁気マイクロアレイ上に導入し、洗浄後、基板表面の顕微鏡観察を行った。その結果、磁性ドットが基板面より突き出て埋め込まれた基板Aではその突き出た磁性ドットの側面に細胞がトラップされ、また基板面と同じ高さで埋め込まれた基板Bでは磁性ドットの上に細胞が観察された。一方、埋め込まれた高さが基板面に満たない基板Cでは細胞のトラップは観察されず、チェーン状の未反応磁気ナノ粒子の凝集体(1マイクロ程度)がドット内に突き刺さっているような形で観察された。以上の結果より、基板面と同じ高さで埋め込まれたCoNiFe面内軟磁性体の磁気マイクロアレイを用いることにより、1つの細胞のトラップが可能であることが実証された

1細胞のマニュピュレーション技術として、磁気マイクロドットアレイによる細胞トラップ技術を開発した。(1) 磁性材料の細胞生育への影響本研究では、アレイに用いる磁性素材として、CoMFe系磁性膜を選択した。Si基板上に成膜した磁性膜の細胞毒性を評価した結果、24時間後においても磁性膜基板を導入した細胞において生育が観察され、細胞への毒性が低いことが示唆された。(2) 細胞への磁気標識細胞への磁性化として、B細胞系のRaji細胞(CD19陽性細胞)及び磁性細菌が合成するProtein G発現磁気ナノ粒子を用いた。Raji細胞へ特異的に磁気標識が行えているかを確認するために、Cy3及び抗GD19抗体を導入した磁気ナノ粒子を細胞に標識した後、Alexa488-抗CD19抗体を導入した。洗浄後の細胞についてCy3及びAlexa488の蛍光をもとに1細胞表面の磁気ナノ粒子の分布を解析した結果、抗原部位と磁気ナノ粒子の局在部位に関して93.3%の重複が確認された。(3) 末梢血からの標的細胞の磁気分離末梢血からの直接的な磁気細胞分離を試みた。B細胞及びT細胞の表面抗原(CD19, CD20, CD3)に対する抗体をそれぞれ磁気ナノ粒子に固定化後、末梢血に希少な割合でしか含まれていない細胞を分離した。その結果、磁気ナノ粒子は他の細胞に非特異的に結合することなく、90%以上の高純度において磁気分離できることが示された。(4) 磁性ドットアレイを用いた細胞トラップSi基板上にマイクロパターン技術を用いてドット径、ドット間距離を変えたマイクロアレイを作製し、無電解めっき法により磁性ドットアレイの作製に成功した。MFeB磁石の上にアレイを設置し、磁気ビーズとしてSpherobeads、また磁気ナノ粒子で標識した細胞をマイクロアレイ上に導入することに成功した

物質のキラリティの研究は、アミノ酸、タンパク質、DNAなどの生体物質の構造と機能性の関係の解明、薬剤の効用と副作用の研究などに有用となる物質科学における緊要な学際的研究である。われわれは、直線複屈折、直線2色性、円複屈折、円2色性を同時に測定できる光学測定法（拡張HAUP法）を開発し、2それら異方的光学物理量の分光学的測定及び温度依存性の測定を可能とした「一般型高精度万能旋光計」(Generalized-HAUP、略称、G-HAUP)の開発に成功した。本研究では、その測定原理をイメージング技術に応用して、新しい顕微鏡「キラル・磁気光学ハイブリッド顕微鏡」を創設ために不可欠な光学系の改良ならびに測定プログラムの開発やその実証に必要な実験を遂行することとした。さらに、シンクロトロン放射光を用いた「キラル・磁気光学ハイブリッド顕微鏡」の開発への試験的な研究に着手することとした。まずは、キラル光学効果の高分解能分光測定及び2次元イメージングのできる「透過型高分解能キラリティ顕微鏡」を試作するため、G-HAUPの光学系及びその駆動系、試料台、検出器、ノイズ低減機構、測定及びデータ解析プログラムを改良した。次いで、その新しい光学系と測定プログラムを用いて、サリドマイドのキラル反転機構の解明に資するキラル光学的研究を行った。サリドマイドはキラルな分子構造を有するきわめて有用な薬剤であるが，溶液状態ではR体からS体，S体からR体へキラル反転することが指摘され、その機構は未だ十分理解されていない。一方、サリドマイドのキラル光学性質を測定し、その結果の正当性を確保するためには、サリドマイドのキラル結晶の構造を決定することが重要である。そこで、まず、我々はこれまで明らかとなっていないサリドマイドのキラル結晶につき、X線回折法を用いて構造解析した。サリドマイドの結晶はキラルな点群C2となり、2つのサリドマイド分子が環状水素結合して安定な構造を有していることが明らかとなった。さらに，G-HAUPを用いてサリドマイドのキラル結晶の光学的性質の波長依存性を調べたところ、再現性を確認する必要はあるものの、直線複屈折、直線2色性、円複屈折、円2色性の異常を見い出すことができた。